Sanctum is a tower defense computer game where the main character, Skye, must eliminate an army of strange aliens to save her homeland of Elysion One. In this game, the player builds defensive and offensive towers. They are built beside the path that enemies use to advance to the player's base. These towers act as a defense by attacking the enemies that walk on the path. At the start, the player chooses 8 towers. These 8 towers range from attackers to teleporters. When the towers kill the enemies, points are earned. These points are used to purchase upgrades to the tower. These upgrades can make the towers stronger. Additionally, the player can gain access to more advanced towers during the course of the game. The enemies that are not killed keep moving forward to the player's base (core). At the start, the core's health is at 100%. It is reduced whenever an enemy reaches it. When it reaches 0%, game over happens.
The game also has elements of first-person shooting. The player can move around the stage to personally kill the enemies. There are a variety of enemies in Sanctum. Some of them are airborne. Some are on land. Because of that, certain towers are effective against one class of enemies while ineffective with other types.